Genomic Landscape of Prostate Cancer Differs by Ancestry, but Frequency of Actionable Alterations Is Similar

The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Oncology Nurse Advisor‘s conference coverage.

Rates of actionable genetic alterations were similar in prostate cancer patients with African ancestry and those with European ancestry, according to results of a large-scale genomic analysis presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

These results were presented by Brandon A. Mahal, MD, of the University of Miami Sylvester Comprehensive Cancer Center.

Dr Mahal noted that patients of African ancestry have a higher burden of prostate cancer when compared with patients of European ancestry. This may be a result of differences in socioeconomic factors, environmental exposures, and biologic or epigenetic phenomena.

“We sought to characterize the genomic landscape, comprehensive genomic profiling utilization, and treatment patterns based on genomic ancestry in an effort to better understand advanced prostate cancer,” Dr Mahal said.

He and his colleagues analyzed samples from 11,741 patients with advanced prostate cancer who had undergone comprehensive genomic profiling (CGP) by Foundation Medicine as part of their routine care.

Genomic ancestry was determined using a single nucleotide polymorphism-based approach, which revealed that 12% of patients had African ancestry and 79% had European ancestry.

Patients with African ancestry had a median lower age at diagnosis compared with patients who had European ancestry — 64 years and 67 years, respectively. Only 4.2% of patients with African ancestry and 2.5% with European ancestry were younger than age 50.

The frequency of targetable alterations was similar between the groups — 22.1% in patients of African ancestry and 22.4% in patients of European ancestry. The frequency of alterations in DNA damage response pathway genes was also similar — 17.8% and 18.7%, respectively.

However, patients of African ancestry had a lower frequency of alterations in TP53, PTEN, and TMPRSS2-ERG, and they had a greater frequency of alterations in SPOP, CDK12, CCND1, KMT2D, HGF, and MYC. 

The researchers also evaluated clinical characteristics and treatment patterns by ancestry in another data set. They analyzed data from the Flatiron Health-Foundation Medicine clinico-genomic database, which included 841 patients with metastatic or castrate-resistant prostate cancer.

In this cohort, patients of African ancestry (n = 79) were more likely than patients of European ancestry (n = 762) to be treated in a community practice — 91% and 63%, respectively.

CGP was utilized later in the course of treatment among patients of African ancestry than among patients of European ancestry — after a median of 2 lines of therapy and 1 line of therapy, respectively.

The types of therapy used were largely similar between the groups. However, clinical trial drug use was lower among patients of African ancestry, with 11% receiving a study drug, compared with 30% of patients who had European ancestry.

“These findings suggest that intrinsic biological differences are unlikely to be a major driver of ancestry-based disparities in outcomes among men diagnosed with advanced prostate cancer,” Dr Mahal concluded.

He added that the differences in the timing of CGP utilization and clinical trial enrollment “may potentially impact the genomic landscape, outcomes, and ultimately disparities.”

Disclosures: This research was supported by Foundation Medicine. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Oncology Nurse Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.

Reference

Sivakumar S, Lee JK, Moore JA, et al. Ancestral characterization of the genomic landscape, comprehensive genomic profiling utilization, and treatment patterns may inform disparities in advanced prostate cancer: a large-scale analysis. J Clin Oncol. 2021;39:(suppl 15; abstr 5003). doi:10.1200/JCO.2021.39.15_suppl.5003

This article originally appeared on Cancer Therapy Advisor